rs1339951

Variant names:

• chr1-196513227-C-A
• rs1339951
• NM_198503.5:c.96-20886G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198503.5(KCNT2):​c.96-20886G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 152,112 control chromosomes in the GnomAD database, including 56,454 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.85 (56454 hom., cov: 33)
• Consequence: KCNT2 NM_198503.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911
• Publications: 2 publications found

Genes affected

KCNT2 (HGNC:18866): (potassium sodium-activated channel subfamily T member 2) Enables chloride-activated potassium channel activity. Involved in potassium ion export across plasma membrane. Located in plasma membrane. Implicated in developmental and epileptic encephalopathy 57. [provided by Alliance of Genome Resources, Apr 2022]

KCNT2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 57

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198503.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT2	NM_198503.5	MANE Select	c.96-20886G>T		intron	N/A	NP_940905.2
	KCNT2	NM_001287819.3		c.96-20886G>T		intron	N/A	NP_001274748.1	Q6UVM3-2
	KCNT2	NM_001287820.3		c.96-20886G>T		intron	N/A	NP_001274749.1	Q6UVM3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNT2	ENST00000294725.14	TSL:1 MANE Select	c.96-20886G>T		intron	N/A	ENSP00000294725.8	Q6UVM3-1
	KCNT2	ENST00000367433.9	TSL:1	c.96-20886G>T		intron	N/A	ENSP00000356403.5	Q6UVM3-2
	KCNT2	ENST00000609185.5	TSL:1	c.96-20886G>T		intron	N/A	ENSP00000476657.1	Q6UVM3-3

Frequencies

GnomAD3 genomes AF: 0.855 AC: 129928 AN: 151994 Hom.: 56429 Cov.: 33

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.975

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.884

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.855 AC: 130002 AN: 152112 Hom.: 56454 Cov.: 33 AF XY: 0.858 AC XY: 63775 AN XY: 74350

African (AFR) AF: 0.684 AC: 28371 AN: 41462

American (AMR) AF: 0.922 AC: 14070 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.975 AC: 3380 AN: 3468

East Asian (EAS) AF: 0.985 AC: 5099 AN: 5178

South Asian (SAS) AF: 0.985 AC: 4754 AN: 4826

European-Finnish (FIN) AF: 0.862 AC: 9127 AN: 10586

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62138 AN: 68006

Other (OTH) AF: 0.885 AC: 1871 AN: 2114

Alfa AF: 0.898 Hom.: 52770

Bravo AF: 0.852

Asia WGS AF: 0.962 AC: 3345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.35
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1339951; hg19: chr1-196482357;